Workflow for high-throughput analysis of analytes in liquid samples

Abstract

Methods of detecting at least one analyte in at least one liquid sample are described. The method includes the steps of desalting the liquid sample, acoustically ejecting the desalted sample into an open-port interface, diluting the desalted sample, and transferring the diluted sample to an ionization source, ionizing the diluted sample, and selecting ions of interest by ion mobility

1 . A method of detecting at least one analyte in at least one liquid sample, the method comprising the steps of:
 desalting the liquid sample,   acoustically ejecting the desalted sample into an open-port interface, diluting the desalted sample, and transferring the diluted sample to an ionization source,   ionizing the diluted sample, and   selecting ions of interest by ion mobility.   
     
     
         2 . The method of  claim 1 , wherein the liquid sample is selected from the group consisting of urine, blood, oral fluid, and plasma. 
     
     
         3 . The method of  claim 1 , wherein the desalted sample is diluted at a low-fold ratio. 
     
     
         4 . The method of  claim 3 , wherein the low-fold ratio is a 10-fold dilution or less. 
     
     
         5 . The method of  claim 1 , wherein the desalted sample is diluted at a high-fold ratio. 
     
     
         6 . The method of  claim 5 , wherein the high-fold ratio is greater than a 10-fold dilution. 
     
     
         7 . The method of  claim 1 , wherein selecting ions of interest is conducted using a differential mobility spectrometer. 
     
     
         8 . The method of  claim 7  wherein the differential mobility spectrometer includes flat or curve electrodes. 
     
     
         9 . The method of  claim 7 , wherein the differential mobility spectrometer separates coeluting compounds, isobaric compounds, isomeric compounds, constitutional isomers, or diastereomers from the ions of interest. 
     
     
         10 . The method of  claim 1 , wherein the desalting step is conducted using reverse phase or anion exchange phases or size-exclusion, molecular sieve, a pipette tip, and/or gel filtration. 
     
     
         11 . The method of  claim 1 , wherein the desalting step is conducted with an inline desalting device. 
     
     
         12 . The method of  claim 11 , wherein the inline desalting device is a column or a cartridge. 
     
     
         13 . The method of  claim 11 , wherein a liquid handler houses the inline desalting device. 
     
     
         14 . The method of  claim 13 , wherein the liquid handler also houses an acoustic droplet ejection transducer. 
     
     
         15 . The method of  claim 1 , wherein the method further comprises hydrolyzing the desalted sample to produce a hydrolysate and the step of acoustically ejecting the desalted sample comprises acoustically ejecting the hydrolysate into the open port interface. 
     
     
         16 . The method of  claim 1 , wherein after selecting the ions of interest, the method further comprises mass analyzing the ions of interest. 
     
     
         17 . The method of  claim 16 , wherein the ions of interest are mass analyzed with a mass spectrometer. 
     
     
         18 . The method of  claim 16 , further comprising the step of quantifying the amount of the analyte in the liquid sample. 
     
     
         19 . The method of  claim 18 , wherein the limit of quantification is in a low ng/mL range. 
     
     
         20 . The method of  claim 18 , wherein the limit of quantification is in a sub ng/mL range. 
     
     
         21 . The method of  claim 1 , wherein the method further employs a multiplexing assay to analyze multiple liquid samples. 
     
     
         22 . The method of  claim 21 , wherein about three samples per second are analyzed. 
     
     
         23 . The method of  claim 16 , wherein the method is used in a high-throughput screening application or a rapid screening workflow. 
     
     
         24 . The method of  claim 1 , wherein the analyte is at least one drug of abuse. 
     
     
         25 . The method of  claim 24 , wherein the drug of abuse is selected from the group consisting of amphetamines, methamphetamines, benzodiazepines, barbiturates, LSD, ecstasy, marijuana, cocaine, PCP, methadone, stimulants, and opioids (narcotics).